The Diamond Blackfan Anemia Registry (DBAR) is a comprehensive database of patients with the rare inherited bone marrow failure syndrome Diamond Blackfan anemia (DBA). DBA is a heterogeneous genetic disorder characterized by pure red cell aplasia, congenital anomalies and a predisposition to cancer. Anemia usually presents in infancy or early childhood and approximately 50% of patients have at least one congenital anomaly. The actuarial cancer risk although increased, is as of yet, undetermined. To date six genes encoding ribosomal proteins, of both the small and large subunits, have been found to be mutated, representing nearly 50% of patients with DBA. Of note, "affected" individuals within the same family may vary dramatically as to the degree of anemia, response to corticosteroids, the presence of congenital anomalies and the development of cancer. Prior to the development of the DBAR our knowledge regarding the epidemiology and response to various treatment modalities was determined exclusively from literature reports. The DBAR has been developed in order to provide a well-characterized patient substrate linked to biological samples, permitting the study of the epidemiology and biology of DBA. The objective of this application is to improve and exploit the DBAR in order to: 1) facilitate investigations into the epidemiology and biology of DBA;2) provide an accurate phenotype of DBA patients to facilitate genotype-phenotype correlations;3) provide access of well characterized patients to treatment protocols;4) provide patients and their health care providers access to research studies;5) provide patients and their health care providers with results of research studies;6) serve as a resource to patients and their doctors to guide diagnostic, therapeutic, and reproductive decisions;7) develop an accurate and rapid diagnostic screening test for DBA;and 8) encourage national and international collaborative research. PUBLIC HEALTH RELEVANCE: By exploiting a well-characterized patient population, the Diamond Blackfan Anemia Registry, the molecular basis of red blood cell production and its link to ribosome assembly and function and cancer predisposition, can be explored. The goal of this project is to utilize this database for detailed analysis of the degree of anemia, treatment response, and presence of congenital anomalies and development of cancer in DBA patients. This will lead to insights into the etiology of birth defects and cancer in these patients and in the population at large and ultimately lead to improved clinical care for DBA patients.